The present invention relates to the compound 1-2-(6-chloro-2,3-dihydro-2-oxo -1H-indol-5-yl)ethyl!-4-imino(2-mercaptophenyl)methyl!piperazine or one of its pharmaceutically acceptable salts, to processes for its preparation, to pharmaceutical compositions and to methods of treatment. 1-2-(6-Chloro-2,3-dihydro-2-oxo-1H-indol -5-yl)ethyl!-4-imino(2-mercaptophenyl)methyl!piperazine is a pro-drug of 5-(2-(4-(1,2-benzisothiazol-3-yl)-1-piperazinyl)ethyl)-6-chloro-1 ,3-dihydro-2H-indol-2-one (hereinafter referred to as ziprasidone). The compound of the invention, 1-2-(6-chloro -2,3-dihydro-2-oxo-1H-indol-5-yl)ethyl!-4-imino(2-mercaptophenyl)methyl! piperazine, has neuroleptic activity and is therefore useful as an antipsychotic.
The aqueous solubility of the dihydrochloride salt of 1-2-(6-chloro-2,3-dihydro-2-oxo-1H-indol-5-yl)ethyl!-4-imino(2-mercaptop henyl)methyl!piperazine at about 25.degree. C. is about 25 mg/mL which is approximately 300 times higher than ziprasidone hydrochloride (8.0 .mu.g/mL).
U.S. Pat. No. 4,831,031, issued May 16, 1989, which is hereby incorporated by reference in its entirety, discloses 5-(2-(4-(1,2-benzisothiazol-3-yl)-piperazinyl)ethyl)6-chloro-1,3-dihydro-2 H-indol-2-one hydrochloride, which has the formula ##STR1## wherein Ar is benzisothiazol-3-yl, in the hemihydrate form (hereafter "the hemihydrate").
U.S. Pat. No. 5,312,925 issued May 17, 1994, which is hereby incorporated by reference in its entirety, refers to the monohydrate hydrochloride salt of ziprasidone, processes for its preparation, and pharmaceutical compositions and methods of treating psychotic disorders.
U.S. Pat. No. 5,359,068, issued Oct. 25, 1994, which is hereby incorporated by reference in is entirety, refers to processes and intermediates for the preparation of ziprasidone.
U.S. Pat. No. 5,206,366, issued Apr. 27, 1993, which is hereby incorporated by reference in its entirety, refers to an aqueous based process for preparing ziprasidone.
U.S. Patent Application 60/006,301, filed Nov. 7, 1995, refers to the preparation of 1-(1,2-benzisothiazol-3-yl)piperazine which is a key intermediate in the preparation of ziprasidone.